Flores, who was educated in the United States, was President from 1999 and 2004. He was found unconscious at his home and taken to a hospital in San Salvador, his attorney Edgar Morales Joya said.
He suffered a stroke last week that caused irreversible brain damage. At the time, Flores he was under house arrest battling corruption charges.
In December, a judge sent Flores to trial on charges of embezzlement, money laundering, disobedience to individuals and illicit or unjust enrichment.
Flores had maintained he was innocent.
In January 2015, the ex-President admitted to a special commission of the Salvadoran Congress that he received contributions from Taiwan when he was a candidate and during his tenure but insisted the money was used for social works.
"I never received a donation for me, never deposited in any account of mine, never used it personally, never deposited it, never moved it, never used it. It wasn't for me," Flores said.
He said he used funds to combat drug trafficking and gangs and to help those affected by a 2001 earthquake, which buried hundreds of homes in a landslide.
But victims of the disaster have said that's not true.
The Flores case came to light when former President Mauricio Funes revealed a report from the Treasury Department, which considered some transactions suspicious. Funes insisted on further investigation.
Flores defended himself and accused Funes of defaming him.
Current Salvadoran President Salvador Sanchez offered his condolences to Flores' family on Twitter.